MOLECULAR DYNAMICS SIMULATIONS & METHOD DEVELOPMENT: DRUG DESIGN

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We use the Computer Graphics Laboratory facilities to display and analyze the molecular dynamics simulations results. Our research projects focus on a) refining, testing and developing the new generation of additive and nonadditive force field parameters; and b) macromolecular simulation using molecular dynamics. The new approach, based on continuum solvent analysis, has been applied to analyze molecular dynamics trajectories. This new approach provides direct free energies of the solute in the aqueous solution with remarkable accuracy. We have applied this method to analyze trajectories of dodecamer duplex d(CGCGAATTCGCG)2 and its phosphoramidate (N-P) analog in water solution. The continuum solvent analysis quantitatively described the preference of the normal DNA to exist predominately in B form in water solution, whereas the 3' phosphoramidate modified DNA duplex in the A form. This work is undergoing further development of the additive and nonadditive AMBER force field. The nonadditive AMBER parametrization includes nonadditive effects based on atomic polarizabilities and lone pairs interactions.